Over 60% of cancer patients are treated with radiotherapy, yet radiation-induced normal tissue damage can cause organ dysfunction and morbidity. Radiotherapy of CNS tumors is problematic due to potential for diminished neurological function or mental retardation. Our proprietary thrombin-derived TP508 peptide mitigates effects of whole-body nuclear radiation in mice, protecting endothelium, delaying bacteremia, and restoring normal wound healing. TP508 has shown positive results in diabetic foot ulcer and fracture repair trials without adverse effects. Therefore, it has reduced regulatory risk and potential for accelerated development. Our long-term objective is to mitigate radiation effects on brain tissue without protecting cancer cells. Project experiments will determine: 1) the optimal dose and timeline for vascular protection;2) whether TP508 protects brain tissue from radiotherapy damage using intravital microscopy, MRI, and immunohistochemistry;and 3) whether TP508 protection is selective for normal tissue without altering radiation killing of cancer cells using in vitro assays and cancer cell injection into nude mouse brains. Using noninvasive imaging techniques for these early studies adds technological innovation and helps to define future clinical trial endpoints. With successful project completion, we will meet with the FDA and proceed with critical Phase 2 IND-GLP experiments needed to initiate clinical trials.